Fibroblast growth factor (FGF) inhibitors are commonly used to treat certain types of cancers, however new research conducted at Georgetown University Medical Center suggests these drugs may also be a good alternative to currently-available blood pressure medications. While patients diagnosed with hypertension can be treated with a number of different drugs, their mechanisms of action are not suitable for all patients.
Oncologists treat certain cancers using FGF inhibitors to prevent angiogenesis of malignant tissue, cutting off the tumor’s access to oxygen and other nutrients carried in the blood. However, these drugs also have an effect on blood pressure, prompting Georgetown researchers to wonder whether the cancer medications could also be used to treat hypertension.
“It’s rare that a single class of drugs can be used for such different conditions, but that is what our study strongly suggests,” said senior investigator Dr. Anton Wellstein, professor of oncology and pharmacology at Georgetown University School of Medicine and a researcher at Georgetown Lombardi Comprehensive Cancer Center. The researchers published their findings in the journal Hypertension.
The role of the FGF pathway in promoting tumor growth and development was previously identified by Wellstein and his colleagues. Their work also identified FGF binding protein 1 (FGFBP1) that modulates FGF activity when switched on.
In an experiment in mice, Wellstein and his team found that when FGFBP1 was switched on, the subjects’ blood pressure rose significantly. However, in the case of overexpression in cancer, changes in blood pressure attributable to higher rates of angiogenesis are localized to the tumor.
“It actually went up [30 mm Hg] from a normal blood pressure to pretty bad hypertension,” says Wellstein. “It was amazing.”
When they investigated the mechanism further, they found that overexpression of FGFBP1 had the most impact on the ends of blood vessels – known as resistance vessels – which control the rate at which blood enters that tissue. Higher expression of FGFBP1 was associated with increased sensitivity to angiotensin II, a hormone which constricts blood vessels thereby contributing to rising blood pressure.
“FGF can control how sensitive the blood pressure regulation by angiotensin II is,” said Wellstein. “That tells us that if a person has hypertension, it is possible to target FGF signaling because it contributes to maintenance of high blood pressure by altering sensitivity to a major vasoconstrictive hormone, angiotensin II.”
When mice overexpressing FGFBP1 were given an FGF inhibitor, the research team found that the drug was able to reduce vascular sensitivity to angiotensin II, thereby lowering blood pressure. According to Wellstein, the results haven’t yet been confirmed in humans but those experiments will not be difficult to conduct.
“Of course, we can’t say that this tactic will work in humans with hypertension, but it will be straightforward to test this rather surprising possibility to target a new mechanism of blood pressure control,” said Wellstein.
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